The long-term goal of this project is to identify and characterize the molecular mechanisms by which chemicals induce tumors. Attention is focused on better understanding the role of altered nucleic acids in this process. Primary efforts are directed towards the aromatic amines. Since these carcinogens must undergo metabolic activation in order to react with tissue macromolecules, the identification and characterization of these pathways are specific aims of this project. The transient nature of the reactive species involved dictates that the responsive tissues be the targets of the investigation. Within this context, specific attention is beng given, but not limited to, those enzymes that can generate these reactive and, consequently, unstable products from arylhydroxamic acids by N,O-acyltransfer. Knowledge of these acyl-specific enzymes is being utilized in intact cell and tumor induction experiments that are designed to explore the biological importance of these pathways.